[Diagnosis of neurocysticercosis in patients with epilepsy living in the south-western Dominican Republic]. / Diagnóstico de neurocisticercosis en pacientes con epilepsia residentes en el suroeste de la República Dominicana.

INTRODUCTION: Neurocysticercosis (NCC), a possible cause of epilepsy with limited epidemiological data in the Dominican Republic, is endemic in four provinces in the country's south-western region. This study aimed to determine the association between NCC and epilepsy among people living in these endemic regions, and to obtain preliminary data on the prevalence of NCC in these provinces. PATIENTS AND METHODS: A case-control design was used, consisting of 111 patients with epilepsy with unknown causes, and 60 controls without epilepsy or NCC. The diagnosis of NCC was based on computed tomography and magnetic resonance imaging of the skull, as well as Western immunoblotting for serum antibodies using Taenia solium, following the criteria of Del Brutto et al. RESULTS. NCC was found in 27% of the epileptic patients (n = 30/111) and in 5% of the controls (n = 3/60); the probability of the epileptic patients having NCC was seven times higher than the controls (odds ratio = 7.04, 95% confidence interval: 2.04-24.18; p < 0.001). The participants' sociodemographic characteristics, including their age, sex, level of education, occupation, and province of residence presented no statistical significance in terms of their association with NCC. CONCLUSIONS: This study suggests that NCC is strongly associated with epilepsy in the south-western region of the Dominican Republic, and highlights the need for public health measures to improve the prevention, diagnosis and treatment of both diseases.

TITLE: Diagnóstico de neurocisticercosis en pacientes con epilepsia residentes en el suroeste de la República Dominicana.Introducción. La neurocisticercosis (NCC), una posible causa de epilepsia con datos epidemiológicos limitados en la República Dominicana, es endémica en cuatro provincias de la región suroeste. El objetivo de este estudio fue determinar la asociación entre la NCC y la epilepsia en personas que viven en estas regiones endémicas, así como obtener datos preliminares sobre la prevalencia de NCC en estas provincias. Sujetos y métodos. Se utilizó un diseño de casos y controles compuesto por 111 pacientes con epilepsia de causa desconocida y 60 controles sin epilepsia ni NCC. El diagnóstico de NCC se basó en la tomografía computarizada y la resonancia magnética del cráneo, así como en el inmunotransferencia de Western para anticuerpos séricos contra Taenia solium, siguiendo los criterios de Del Brutto et al. Resultados. Se encontró NCC en el 27% de los pacientes con epilepsia (n = 30/111) y en el 5% de los controles (n = 3/60); los casos de epilepsia tenían siete veces más probabilidades de tener NCC que los controles (odds ratio = 7,04, intervalo de confianza al 95%: 2,04-24,18; p < 0,001). Las características sociodemográficas de los participantes, como la edad, el sexo, el nivel de escolaridad, la ocupación y la provincia de residencia no mostraron significación estadística en cuanto a la asociación con NCC. Conclusiones. Este estudio sugiere que la NCC está fuertemente asociada con la epilepsia en la región suroeste de la República Dominicana, y destaca la necesidad de medidas de salud pública para mejorar la prevención, el diagnóstico y el tratamiento de ambas enfermedades.

Re-Epithelialization of Neuropathic Diabetic Foot Wounds with the Use of Cryopreserved Allografts of Human Epidermal Keratinocyte Cultures (Epifast).

The application of tissue-engineering technology to wound healing has become an option for the treatment of diabetic foot ulcers (DFU). A comparative, prospective study was conducted to assess the efficacy of a cryopreserved allograft of human epidermal keratinocytes (Epifast) to enhance wound healing in granulating DFU. Eighty patients were assigned to receive Epifast (n = 40) or Standard Care (SC) treatment (n = 40). The Epifast group displayed a shorter duration of the epithelialization phase (3.5 ± 4 vs. 6.4 ± 3.6 weeks, p < 0.05) and upon the entire wound healing process than the SC group (10 ± 5.7 vs. 14.5 ± 8.9 weeks, p < 0.05), reaching wound closure at 16 and 30 weeks, respectively. The Kaplan−Meier analysis revealed that Epifast group patients were 50% more likely than the SC to heal wounds faster (Cox-hazards ratio of 0.5, 95% CI = 0.3−0.8, p < 0.0001; Likelihood Ratio of 7.8. p < 0.05). Patients in the control group displayed a slower healing as the Saint Elian (SEWSS) severity grade increased (group differences of 0.6, 3.8, and 4.3 weeks for grades I, II, and III, respectively). DFW treated with Epifast displayed a shorter time to complete re-epithelialization than wounds treated with standard care.

The latin american Saint Elian wound score system (sewss) for the triage of the diabetic foot attack.

To review the global and regional contributions of the Saint Elian Wound Score System (SEWSS) for the diabetic foot syndrome are the aim of this report. The update includes definitions, classification, diagnosis, treatment, prognosis, and prevention to reduce amputations and mortality. From its local use in Mexico to their global spread as part of the Clinical Practice Recommendations of the Diabetic Foot - International Diabetes Federation-2017, the SEWSS has achieved a significant acceptance for the diabetic foot problem care in Latin America. The concept includes the triage of severity grades system for the five types of Diabetic Foot Attack (DFA) due to ischemia, infection, edema, neuropathy (Charcot), or a mixed combination. Persons with Diabetes Mellitus may progress from the low-risk stage to foot attack that may remite to a high risk stage or conversely, evolve to a major amputation or death. The DFA progressive stages (I-III) are described in this review. The clinical details provided by the assessment of the 10 Saint Elian factors permit a rationale therapeutic approach with relevance in prevention and medical treatment and not focused only on wound care avoiding bias originated by specialty-related preferences.

El propósito de este informe es revisar las contribuciones regionales y mundiales del Sistema de San Elian para el Síndrome del Pie Diabético. Esta actualización incluye definiciones, clasificación, diagnóstico, pronóstico, tratamiento y prevención para reducir las amputaciones y su mortalidad. Desde su aplicación local en Mexico hasta su difusión mundial como parte fundamental de las Recomendaciones de Práctica Clínica del Pie Diabético- Federación Internacional de Diabetes 2017, el sistema ha alcanzado una aceptación significativa para la atención del Pie Diabético en Latinoamérica. El concepto incluye el triage urgente por la diferenciación de la gravedad que proporciona el sistema para los cinco tipos de Ataque Del Pie Diabético (APD): isquemico, infeccioso, edema grave, neuropatia (Charcot) y el mixto. Los pacientes con DM-2 pueden evolucionar desde un pie con bajo riesgo hasta un APD que logre remitir a una etapa de riesgo alto o que finalmente evolucione a amputacion mayor y/o muerte. Se describen las etapas evolutivas (I-III). La detallada evaluación que proporciona los 10 factores de San Elian permiten un abordaje terapéutico racional con relevancia en la prevención y el tratamiento médico sin centrarse erróneamente en el cuidado de heridas.

Androgen Deprivation Therapy in Patients With Prostate Cancer Increases Serum Levels of Thromboxane A2: Cardiovascular Implications.

Introduction: Androgens have been described as important players in the regulation of vascular function/structure through their action on the release and effect of vasoactive factors, such as prostanoids. Patients with prostate cancer (PCa) under androgen deprivation therapies (ADTs) present increased risk of cardiovascular mortality. Since thromboxane A2 (TXA2) is one of the most studied prostanoids and its involvement in different cardiovascular diseases has been described, the aim of this study was to investigate: (i) the effect of ADT on the serum levels of TXA2 in PCa patients and its possible link to the redox status and (ii) the effect of the non-hydrolyzable TXA2 analog U-46619 on the function of the aorta of male rats. Methods: The levels of TXA2 and total antioxidant status in 50 healthy subjects, 54 PCa patients, and 57 PCa under ADT were evaluated. These determinations were accompanied by levels of testosterone and C-reactive protein as an inflammation marker. In aortic segments from male rats, the U46619-induced effects on: (i) the vasomotor responses to acetylcholine (ACh), to the NO donor sodium nitroprusside (SNP), to the carbon monoxide-releasing molecule-3 (CORM-3), and to noradrenaline (NA) and (ii) the expression of cyclooxygenase-2 (COX-2), heme oxygenase-1 (HO-1), and phosphorylated ERK1/2 were analyzed. Results: The serum level of TXA2 in patients with PCa was increased with respect to healthy subjects, which was further increased by ADT. There was no modification in the total antioxidant status among the three experimental groups. In aortic segments from male rats, the TXA2 analog decreased the endothelium-dependent relaxation and the sensitivity of smooth muscle cells to NO, while it increased the vasoconstriction induced by NA; the expression of COX-2, HO-1, and pERK1/2 was also increased. Conclusions: ADT increased, along with other inflammatory/oxidative markers, the serum levels of TXA2. The fact that TXA2 negatively impacts the vascular function of the aorta of healthy male rats suggests that inhibition of TXA2-mediated events could be considered a potential strategy to protect the cardiovascular system.

Effects of tadalafil once daily or on demand versus placebo on time to recovery of erectile function in patients after bilateral nerve-sparing radical prostatectomy.

PURPOSE: We report time to erectile function (EF)-recovery data from a multicenter, randomized, double-blind, double-dummy, placebo-controlled trial evaluating tadalafil started after bilateral nerve-sparing radical prostatectomy (nsRP). METHODS: Patients ≤68 years were randomized post-nsRP 1:1:1 to 9-month double-blind treatment (DBT) with tadalafil 5 mg once daily (OaD), 20 mg tadalafil on demand ("pro-re-nata"; PRN), or placebo, followed by 6-week drug-free washout (DFW) and 3-month open-label OaD treatment. Secondary outcome measures included Kaplan-Meier estimates of time to EF-recovery (IIEF-EF ≥ 22) during DBT (Cox proportional hazard model adjusting for treatment, age, and country). RESULTS: A total of 423 patients were randomized to tadalafil OaD (N = 139), PRN (N = 143), and placebo (N = 141); 114/122/155 completed DBT. The proportion of patients achieving IIEF-EF ≥22 at some point during DBT with OaD, PRN, and placebo was 29.5, 23.9, and 18.4 %, respectively. DBT was too short to achieve EF-recovery (IIEF-EF ≥ 22) in >50 % of patients; median time to EF-recovery was non-estimable. Time for 25 % of patients to achieve EF-recovery (95 % CI) was 5.8 (4.9, 9.2) months for OaD versus 9.0 (5.5, 9.2) and 9.3 (9.0, 9.9) months for PRN and placebo, respectively. Showing a significant overall treatment effect (p = 0.038), the probability for EF-recovery was significantly higher for OaD versus placebo [hazard ratio (HR); 95 % CI 1.9; 1.2, 3.1; p = 0.011], but not for PRN versus placebo (p = 0.140). Of 57 OaD patients (41.0 %) with ED improved (by ≥1 IIEF-EF severity grade) at the end of DBT, 16 (28.1 % of 57) maintained this improvement through DFW and 27 (47.4 %) declined but maintained improvement from baseline after DFW. CONCLUSIONS: Data suggest that the use of tadalafil OaD can significantly shorten the time to EF-recovery post-nsRP compared with placebo.

Leaching in metal nanoparticle catalysis.

Since the discovery of catalysis, the identification of the different species in the mechanism involved in the reaction has been a challenge. When nanocatalysis entered the scene, the detection of material that came out from solutions attracted the attention and raised several questions: was this solid part of the nanocatalyst? was it the precursor of the nanocatalysts (the so-called precatalyst)? or was it the nanocatalyst itself? The discussion focuses on whether the catalysis is determined by the species that exist in solution or if it is generated from the support and hence the catalytic reaction is carried out with these soluble species. Furthermore, it appears that leaching is a phenomenon which occurs mainly in palladium- catalyzed reactions and that involves palladium nanoparticles (NPs). The research, findings and patents in the leaching process in catalytic reactions are reviewed in the present paper.

Bioética do Sistema Único de Saúde/SUS: uma análise pela bioética da proteção

O trabalho aborda, do ponto de vista da bioética da proteção, o tema do conflito entre os três princípios morais e políticos norteadores do SUS: direito à igualdade, integralidade na assistência à saúde e universalidade do acesso.

Diagnóstico, clasificación y tratamiento de las infecciones en el pie diabético / Diagnosis, classification, and treatment of infections in the diabetic foot

Objetivo: Revisar la literatura para establecer lineamientos y recomendaciones para disminuir la amputación y muerte relacionadas con las infecciones del pie diabético. Sede: Centro de Prevención y Salvamento de Pie Diabético San Elian, Veracruz, Veracruz. Diseño: Revisión de la literatura. Material y Métodos: Se realizó una búsqueda en la literatura para la respuesta adecuada de los siguientes ejes de investigación: clasificación de la infección (cómo se determina la gravedad de la infección); importancia de clasificar (cómo se define una infección grave, qué puntaje tiene la osteomielitis en la gravedad de la infección), y tratamiento (momento óptimo, tratamiento no quirúrgico, uso de antibióticos, cultivos, manejo de osteomielitis y tiempo de tratamiento). Resultados: Las clasificaciones de PEDIS (Perfusión, extensión, profundidad, infección y sensibilidad), IDSA (Infectious Disease Society of America) y San Elian clasifican la gravedad de la infección en leve, moderada y grave. La desbridación quirúrgica de tejido infectado debe realizarse sin diferimiento en forma inicial y subsecuente tantas veces como sea necesario con ''destechamiento'' de trayectos fistulosos. En las infecciones de moderadas a graves se recomienda tratamiento empírico de amplia cobertura (Gram positivos, Gram negativos y anaerobios). El cultivo de la herida antes de iniciar o continuar el tratamiento empírico se hace en infecciones moderadas o graves y se ajusta con el resultado del cultivo si no mejora o empeora la infección. El Staphylococcus aureus se aísla en un 40 y 50 %, con resistencia a la meticilina en un 30 a 40 %. Los antibióticos de elección son la vancomicina, la tigeciclina o el linezolid. La osteomielitis es una infección moderada profunda, caracterizada por descarga purulenta, exposición del hueso, ''dedo en salchicha'', o prueba del estilete positivo. El diagnóstico definitivo se hace con biopsia o resonancia magnética nuclear. La hospitalización está indicada en casos graves en pacientes hemodinámicamente y metabólicamente inestables. Conclusiones: Las infecciones de pie diabético pueden ser de leves a graves y pueden culminar en amputación parcial del pie, de la extremidad o hasta causar la defunción del paciente. Se requiere de una atención sistemática e integral con base en la clasificación y puntaje de San Elian.

Objective: To review the literature to establish guidelines and recommendations to diminish amputation and deaths related to diabetic foot infections. Setting: Centro de Prevención y Salvamento de Pie Diabético San Elian, Veracruz, Veracruz, Mexico. Design: Review of the literature. Material and Methods: We performed a search in the literature to find an adequate answer to the following research questions: classification of the infection (how to determine the severity of the infection), relevance of classifying (how is a severe infection defined, what score can be given to osteomyelitis in the severity of the infection) and treatment (optimal time, non-surgical treatment, antibiotics use, handling of osteomyelitis, and time of treatment). Results: PEDIS (perfusion, extension, depth, infection, and sensitivity), IDSA (Infectious Disease Society of America) and San Elian classify the infection as mild, moderate and severe. Surgical debridement of the infected tissue must be performed without delay initially and subsequently as many times as required with ''unroofing'' of fistulous tracts. In moderate to severe infections an ample coverage (Gram positive and Gram negative and anaerobic bacteria) treatment is recommended. Culturing of the injury before or during empirical treatment is performed for moderate to severe infections and should be adjusted to the result of the culture if the infections does not improve or gets worse. Staphylococcus aureus is isolated 40 to 50%, with resistance to methicillin in 30 to 40%. Choice antibiotics are vancomycin, tigecycline and linezolid. Osteomyelitys is a deep moderate infection, characterized by purulent discharge, bone exposure, ''sausage toe'' or positive probe-to bone test. Definite diagnosis is reached with biopsy or magnetic nuclear resonance. Hospitalization is indicated in severe cases of hemodynamically and metabolically unstable patients. Conclusions: Diabetic foot infections can go from mild to severe and end in partial amputation of the feet, the extremity, or even cause death of the patient. Systematic and integral care based on the San Elian classification and score is required.

Measurement of blood flow in arteriovenous malformations before and after embolization using arterial spin labeling.

The assessment of shunt reduction after an embolization of an arteriovenous malformation (AVM) or fistula (AVF) from conventional angiography is often difficult and may be subjective. Here we present a completely non-invasive method using magnetic resonance imaging (MRI) to measure shunt reduction. Using pulsed arterial spin labeling (PASL), we determined the relative amount of signal attributed to the shunt over 1.75 s and 6 different slices covering the lesion. This amount of signal from the shunt was related to the total signal from all slices and measured before and after embolization. The method showed a fair agreement between the PASL results and the judgement from conventional angiography. In the case of a total or subtotal shunt occlusion, PASL showed a shunt reduction between 69% and 92%, whereas in minimal shunt reduction as judged by conventional angiography, the ASL result was -6% (indicating slightly increased flow) to 35% in a partially occluded vein of Galen aneurysm. The PASL method proved to be fairly reproducible (up to 2% deviation between three measurements without interventions). On conclusion, PASL is able to reliably measure the amount of shunt reduction achieved by embolization of AVMs and AVFs.

Prevalence of xenotropic murine leukemia virus-related virus infection in different risk populations in Spain.

Human infection with the xenotropic murine leukemia virus-related virus (XMRV) has been associated controversially with prostate cancer and chronic fatigue syndrome. Information is lacking about the mechanisms of transmission and potential risk groups for XMRV infection. Plasma and peripheral blood mononuclear cells (PBMCs) from individuals with retroviral infections, chronic viral hepatitis, autoimmune diseases, prostate cancer, chronic fatigue syndrome, and blood donors were tested for XMRV markers. Antibodies to XMRV proteins p15E and gp70 were examined using research assays. DNA extracted from PBMCs was tested for the presence of XMRV gag and env sequences. A total of 1103 specimens belonging to individuals with chronic fatigue syndrome and/or fibromyalgia (437), prostate cancer (69), HIV-1 (149), HTLV-1/2 (31), chronic hepatitis B (81), chronic hepatitis C (72), autoimmune diseases (18), and blood donors (246) were examined. Overall, three samples (0.3%) were p15E seroreactive (two HTLV-1 and one HCV patient). Another 15 (1.4%) were gp70 seroreactive (six chronic fatigue syndrome-fibromyalgia, four blood donors, two HIV-1, one prostate cancer, one HBV, and one HCV). Four specimens were initially positive for XMRV gag sequences, but none could be confirmed by repeated testing. In summary, no evidence of XMRV infection was found in populations with retroviral and viral hepatitis infections in Spain. Likewise, XMRV was not recognized in patients with autoimmune diseases, chronic fatigue syndrome-fibromyalgia, prostate cancer, or healthy blood donors.

Immunoreactivity to caspase-3, caspase-7, caspase-8, and caspase-9 forms is frequently lost in human prostate tumors.

Caspases are essential initiators and executioners of apoptosis. Changes in their expression may contribute to the development of proliferative disorders such as cancer, by altering the death-proliferation homeostatic balance. The aim of this work was to analyze the expression of a broad panel of caspases at the epithelial level in human prostate tissues to assess possible prostatic disease-related alterations. We comparatively analyzed by immunohistochemistry the expression of pro-caspase-3, pro-caspase-8, pro-caspase-9, cleaved caspase-3, cleaved caspase-8, and caspase-7, in normal and pathologic (benign hyperplasic, premalignant [high-grade intraepithelial neoplasia], and cancerous [prostate cancer]) human prostate epithelium. Expression of caspases was correlated with clinicopathologic features, including preoperative prostate-specific antigen levels, Gleason scores, and biochemical progression. Percentage of positive samples for all the analyzed caspases decreased in prostate cancer versus normal prostate epithelium. The values obtained for benign prostatic hyperplasia and high-grade intraepithelial neoplasia more qualitatively resembled those of the prostate cancer group. Our results indicate that caspase expression in prostate malignant cells is reduced in a substantial number of patients and that such an alteration occurs in the premalignant stage. Loss of caspase expression could constitute a useful marker for prostate cancer diagnosis. Therapeutic approaches aimed to recover or enhance caspase expression might be effective against prostate cancer.

Relationship between IL-6/ERK and NF-κB: a study in normal and pathological human prostate gland.

BACKGROUND: There is growing evidence that inflammation is a causal factor in cancer, where pro-inflammatory cytokines such as IL-6, IL-1 or TNF-α could induce cellular proliferation by activation of NF-κB. This study focuses on the IL-6/ERK transduction pathway, its relationship with NF-κB, and the consequences of dysregulation in the development of prostate pathologies such as benign prostate hyperplasia (BPH), prostate intraepithelial neoplasia (PIN) and prostate cancer (PC). METHODS: Immunohistochemical and Western blot analyses for IL-6, gp-130, Raf-1, MEK-1, ERK-1, p-MEK, ERK-2, p-ERK, NF-κB/p-50 and NF-κB/p-65 were carried out in 20 samples of normal prostate glands, 35 samples of BPH, 27 samples with a diagnosis of PIN (low-grade PIN or high-grade PIN), and 95 samples of PC (23 with low, 51 with medium and 21 with high Gleason scores). RESULTS: Immunoreaction to IL-6, gp-130, ERK-1, ERK-2, p-ERK and NF-κB/p50 was found in the cytoplasm of epithelial cells in normal prostate samples; p-MEK was found in the nucleus of epithelial cells; but not expression to Raf-1, MEK-1 and NF-κB/p65. In BPH, all of these proteins were immunoexpressed, while there was increased immunoexpression of IL-6, gp-130, p-MEK, ERK-1, ERK-2 and NF-κB/p50 (cytoplasm). In PC, immunoexpression of IL-6 and gp-130 were similar to that found in BPH; while immunoexpression of Raf-1, MEK-1, p-MEK, ERK-1, ERK-2, p-ERK, NF-κB/p50 (nucleus and cytoplasm), and NF-κB/p65 (nucleus and cytoplasm) was higher than in BPH. CONCLUSION: Translocation of NF-κB to the nucleus in PC and high-grade PIN could be stimulated by the IL-6/ERK transduction pathway, but might also be stimulated by other transduction pathways, such as TNF-α/NIK, TNF/p38, IL-1/NIK or IL-1/p38. Activation of NF-κB in PC could regulate IL-6 expression. These transduction pathways are also related to activation of other transcription factors such as Elk-1, ATF-2 or c-myc (also involved in cell proliferation and survival). PC is a heterogeneous disease, where multiple transduction pathways might alter the apoptosis/proliferation balance. Significant attention should be give to the combination of novel agents directed towards inactivation of pro-inflammatory cytokines than can disrupt tumour cell growth.

A checklist system to score healing progress of diabetic foot ulcers.

The aim of this article was to validate the checklist contribution of 10 factors relevant to healing in order to score the severity of diabetic foot ulcers. A total of 235 patients from January 2007 to January 2009 were scored according to the Saint Elian Wound Score System from mild to severe (1 to 3) in the following categories: location, topographic aspects, and number of affected zones, ischemia, infection, edema, neuropathy, depth, area, and wound healing phase. The score sum was graded as I (score

Role of IAPs in prostate cancer progression: immunohistochemical study in normal and pathological (benign hyperplastic, prostatic intraepithelial neoplasia and cancer) human prostate.

BACKGROUND: In this study was investigate IAPs in normal human prostate (NP), benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma (PC), and their involvement in apoptosis/proliferation via NF-kB (TNF-alpha, IL-1) stimulation. METHODS: Immunohistochemical and Western blot analyses were performed in 10 samples of normal prostates, 35 samples of BPH, 27 samples diagnosis of PIN (with low-grade PIN or high-grade PIN) and 95 samples of PC (with low, medium or high Gleason grades). RESULTS: In NP, cytoplasm of epithelial cells were positive to c-IAP1/2 (80% of samples), c-IAP-2 (60%), ILP (20%), XIAP (20%); negative to NAIP and survivin. In BPH, epithelial cells were immunostained to c-IAP1/2 (57.57%), c-IAP-2 (57.57%), ILP (66.6%), NAIP (60.6%), XIAP (27.27%), survivin (9.1%). Whereas low-grade PIN showed intermediate results between NP and BPH; results in high-grade PIN were similar to those found in PC. In PC, epithelial cells were immunostained to c-IAP1/2, c-IAP-2, ILP, NAIP, XIAP (no Gleason variation) and survivin (increasing with Gleason). CONCLUSIONS: IAPs could be involved in prostate disorder (BPH, PIN and PC) development since might be provoke inhibition of apoptosis and subsequently cell proliferation. At the same time, different transduction pathway such as IL-1/NIK/NF-kB or TNF/NF-kB (NIK or p38) also promotes proliferation. Inhibitions of IAPs, IL-1alpha and TNFalpha might be a possible target for PC treatment since IAPs are the proteins that inhibited apoptosis (favour proliferation) and IL-1alpha and TNFalpha would affect all the transduction pathway involucrate in the activation of transcription factors related to survival or proliferation (NF-kB, Elk-1 or ATF-2).

Efficacy and safety of neutral pH superoxidised solution in severe diabetic foot infections.

The use of antiseptics in wound care is often controversial and there is definitely a need for a non toxic, highly disinfective agent. This study assessed the efficacy of a neutral pH superoxidised aqueous solution (NpHSS) for infection control, odour reduction and surrounding skin and tissue damage on infected diabetic foot ulcerations. From November 2003 to March 2004, 45 patients with type 2 diabetes were randomised into a single-blind clinical trial comparing NpHSS (intervention group; n = 21) versus conventional disinfectant (control group; n = 16). All patients received comprehensive care including surgical debridement as appropriate, moist wound care, intensive glucose control and broad spectrum antibiotics. Treatment groups were matched in terms of sex, age (61.9 +/- 11.9 versus 67.8 +/- 11.6), years of diabetes duration (16.4 +/- 8.1 versus 17 +/- 10.2), obesity, HgAlc (7.1 +/- 2 versus 6.7 +/- 1.8), initial fasting glycaemia (163 +/- 59 versus 152 +/- 65.8 mg/dl), ulcer duration/week (13.7 +/- 24 versus 15.1 +/- 16.3), B/A Index (0.9 +/- 0.5 versus 1.14 +/- 0.7), depth and extent of infection/periwound cellulitis (groups B and C of the Tampico Hospital Classification) as well as aetiology (P = 0.647). Odour reduction was achieved in all NpHSS patients (100% versus 25%; P < 0.01) and surrounding cellulitis diminished (P < 0.001) in 17 patients (80.9% versus 43.7%). Nineteen patients in the NpHSS group showed advancement to granulating tissue stage (90.4% versus 62.5%; P = 0.05) with significantly less tissue toxicity (94% versus 31.2%; P < 0.01). A non toxic, NpHSS, as part of a comprehensive care regimen, may be more efficacious in infection control, odour and erythema reduction than conventional disinfectants in treatment of diabetic foot infections.

Estudio aleatorizado y comparativo de un apósito de colágeno y celulosa oxidada regenerada en el tratamiento de úlceras neuropáticas de pie diabético / Randomized comparative trial of a collagen/oxidized regenerated cellulose dressing in the treatment of neuropathic diabetic foot ulcers

Introducción. El pie diabético es una complicación de la diabetes mellitus que se manifiesta con la presencia de úlceras que a menudo anteceden a la amputación. Diferentes estudios han comprobado que el entorno de la úlcera neuropática de pie diabético contiene una elevada tasa de metaloproteinasas. El objetivo de este trabajo es evaluar la eficacia de un apósito modulador de proteasas en el tratamiento de úlceras neuropáticas de pie diabético. Material y método. Estudio controlado, aleatorizado y comparativo que incluye a 40 pacientes con úlceras de pie diabético de origen neuropático, con lesiones de una antigüedad superior a 6 semanas. Los pacientes fueron aleatorizados en 2 grupos; el grupo 1 (n = 20) recibió tratamiento con apósito modulador de proteasas y el grupo 2 (n = 20), al que se consideró grupo control, recibió tratamiento de la lesión según protocolo estandarizado. El seguimiento de los pacientes se desarrolló durante 6 semanas. Resultados. Al finalizar las 6 semanas de seguimiento cicatrizaron un total de 12 (63%) de 19 pacientes del grupo 1, de tratamiento con la matriz moduladora, frente a 3 (15%) de 19 pacientes del grupo 2 de control (p < 0,03). La media de tiempo de cicatrización fue de 23,3 ± 9,9 días en el grupo 1 y de 40,6 ± 1,15 días en el grupo 2 (p < 0,01). Conclusiones. El análisis de los resultados obtenidos contrasta la hipótesis de que la utilización de apósitos moduladores de proteasas induce una mejor regeneración tisular que un buen tratamiento local (AU)

Introduction. Diabetic foot is a complication of diabetes mellitus that manifests with the development of ulcers that frequently precede amputation. Several studies have verified that the environment of the diabetic neuropathic foot ulcer contains a high concentration of metalloproteinases. The aim of the present study was to evaluate the efficacy of a protease-modulating dressing in the treatment of neuropathic diabetic foot ulcers. Material and method. A randomized controlled trial was conducted in 40 patients with a 6-week or longer history of neuropathic diabetic foot ulcer. The patients were randomized to two groups: group 1 (n = 20) received treatment with the protease-modulating dressing while the control group (group 2; n = 20) received the treatment specified in the standardized protocol for good wound care. The patients were then followed-up for 6 weeks. Results. After 6 weeks, healing was achieved in 12 patients (63% of n = 19) in group 1 under treatment with the protease-modulating dressing versus three patients (15% of n = 19) in the control group (p < 0.03). The mean time to healing was 23.3 ± 9.9 days in group 1 and 40.6 ± 1.15 days in group 2 (p < 0.01). Conclusions. The results confirm the hypothesis that the use of protease-modulating dressings in patients with neuropathic diabetic foot ulcers leads to better tissue regeneration than good wound care (AU)

[Randomized comparative trial of a collagen/oxidized regenerated cellulose dressing in the treatment of neuropathic diabetic foot ulcers]. / Estudio aleatorizado y comparativo de un apósito de colágeno y celulosa oxidada regenerada en el tratamiento de úlceras neuropáticas de pie diabético.

INTRODUCTION: Diabetic foot is a complication of diabetes mellitus that manifests with the development of ulcers that frequently precede amputation. Several studies have verified that the environment of the diabetic neuropathic foot ulcer contains a high concentration of metalloproteinases. The aim of the present study was to evaluate the efficacy of a protease-modulating dressing in the treatment of neuropathic diabetic foot ulcers. MATERIAL AND METHOD: A randomized controlled trial was conducted in 40 patients with a 6-week or longer history of neuropathic diabetic foot ulcer. The patients were randomized to two groups: group 1 (n = 20) received treatment with the protease-modulating dressing while the control group (group 2; n = 20) received the treatment specified in the standardized protocol for good wound care. The patients were then followed-up for 6 weeks. RESULTS: After 6 weeks, healing was achieved in 12 patients (63% of n = 19) in group 1 under treatment with the protease-modulating dressing versus three patients (15% of n = 19) in the control group (p < 0.03). The mean time to healing was 23.3 +/- 9.9 days in group 1 and 40.6 +/- 1.15 days in group 2 (p < 0.01). CONCLUSIONS: The results confirm the hypothesis that the use of protease-modulating dressings in patients with neuropathic diabetic foot ulcers leads to better tissue regeneration than good wound care.

Interleukin-1 (IL-1alpha and IL-1beta) and its receptors (IL-1RI, IL-1RII, and IL-1Ra) in prostate carcinoma.

BACKGROUND: The principal components of the interleukin-1 (IL-1) family are two secreted factors (IL-1alpha and IL-1beta), two transmembrane receptors (IL-1RI [biologically active] and IL-1RII [inert receptor]), and a natural antagonist receptor of IL-1 function (IL-1Ra). Changes in the expression pattern of these IL-1 members have been reported to be related to disease progression. The objective of the current study was to evaluate these changes in prostatic tissue by means of immunohistochemistry and Western blot analysis. METHODS: Immunohistochemical and Western blot analyses were performed in 20 normal samples, 35 samples of benign prostatic hyperplasia (BPH) and 27 samples from patients with prostate carcinoma (PC). RESULTS: In normal prostate samples, immunoreactions to IL-1beta and IL-1RI were positive, whereas there were no immunoreactions observed to IL-1alpha, IL-1RII, or IL-1Ra. In BPH, in addition to immunoreactions to IL-1beta and IL-1RI, immunoreactions to IL-1alpha, IL-1RII, and IL-1Ra were observed in many samples. In samples of PC with low Gleason grade, most tumors had positive immunoreactions to IL-1alpha and IL-1RI. In samples of PC with high Gleason grade, immunoreactions were seen only to IL-1alpha, IL-1RI, and IL-1RII. CONCLUSIONS: The current results suggested that high expression levels of IL-1alpha and IL1-RI in epithelial cells in BPH and PC samples were involved in cell proliferation and that the loss of immunoexpression of IL-1beta and IL-1Ra was a characteristic feature of PC compared with normal prostate samples and BPH. Because this loss is progressive up to a complete absence of immunoexpression in PC of high Gleason grade, the evaluation of IL-1beta and IL-1Ra in PC may be significant in assessing for malignancy.

Pro-apoptotic tumor necrosis factor-alpha transduction pathway in normal prostate, benign prostatic hyperplasia and prostatic carcinoma.

PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) exerts apoptosis throughout an intracellular transduction pathway that involves the protein kinases TRAF-2 (integration point of apoptotic and survival signals), signal regulating kinase (ASK-1) (pro-apoptotic protein), mitogen activated protein kinase-kinase 4 (MEK-4) (p38 activator and metastasis suppressor gene), Jun N-terminal kinase (JNK) (stress mitogen activated protein kinase) and the transcription factor activator protein-1 (AP-1). MATERIALS AND METHODS: Biopsies from 20 normal, 35 hyperplastic and 27 carcinomatous human prostates were obtained for immunohistochemical and Western blot studies of the mentioned TNF-alpha/AP-1 transduction pathway members. RESULTS: In normal prostates immunoreactions to TRAF-2, ASK-1, MEK-4 and JNK were positive, while no immunoreaction to AP-1 was detected. Although in benign prostatic hyperplasia the percent of immunostained specimens and intensity of immunoreactions to TRAF-2, ASK-1, MEK-4 and JNK decreased, the immunoreaction to AP-1 was positive in 27.3%. In most carcinomatous specimens the immune reaction was negative for all proteins of the TRAF-2/AP-1 pathway. CONCLUSIONS: The TNF-alpha/AP-1 pathway might be a response to the excessive proliferative stimulus, although this response seems to be insufficient to counteract extracellular signals of cell proliferation. In prostate cancer this pathway is probably inactivated by other factors, such as p21 (at the ASK-1 level) or bcl-2 (at the JNK level).

Regulation of proliferation/apoptosis equilibrium by mitogen-activated protein kinases in normal, hyperplastic, and carcinomatous human prostate.

This study investigate the expression of the mitogen-activated protein kinases (MAPKs) in normal prostate, benign prostatic hyperplasia (BPH), and prostatic cancer (PC), and also the possible relationship between the activity of these MAPKs and the apoptosis/proliferation index. Immunochemical techniques were carried out using 2 mouse monoclonal antibodies against human extracellular signal-regulated protein kinase (ERK) and Jun N-terminal kinase (JNK), and 1 goat polyclonal antibody against mouse p38. To compare the results obtained in the 3 specimens, the average percentages of both epithelial and stromal immunostained cells were calculated on immunostained sections. For each of the 3 kinases studied, the percentage of immunostained stromal cells did not change with prostatic alterations. For both ERK and p38, the percentage of immunostained epithelial cells increased significantly in BPH and even more so in PC. For JNK, the percentage of immunostained epithelial cells increased significantly only in PC. These results suggest that ERK could be involved in the elevated proliferation indexes reported in BPH and PC, whereas p38 might contribute to the increased apoptotic index reported in PC. The most probable action of JNK in PC would be cell proliferation stimulation. Overexpression of MAPKs, involved in the development of prostatic hyperplasia and neoplasia, might be secondary to the overexpression of several growth factors.